Abstract There is growing evidence of the therapeutic benefit of targeted modulation of electrical signaling within the network of nerves and ganglia that innervate the organs and tissues of the body (i.e., the PNS). Positive clinical trials are reported for vagal nerve stimulation to treat inflammatory diseases, depression, and epilepsy. Beyond these initial results, a broad range of chronic diseases may be treatable through precise, artificial control of the PNS. Moreover, advanced neuroprotheses hold the promise of restoring lost mobility, dexterity or sensation in the afflicted through long-term, bidirectional connection between the PNS and implantable or externalized hardware. Despite the enormous potential of these therapeutic regimes, progress ? both in basic PNS science and in developing effective interventions to improve human health ? has been hampered by the lack of tools and methods for chronically interfacing with the fine PNS targets in the small animal models in which the foundational pre-clinical research must be done. The objectives of this proposal are the development and characterization of a new peripheral nerve interface that combines soft and stretchable electrodes (Aim 1) with a nerve-anchoring technology that allows intimate, high circumferential contact with a nerve (Aim 2). We anticipate that this novel nerve interface ? the nanoclip stretchable microelectrode array (ncSMEA) ? will be highly compatible with the biomechanics of the PNS and capable of recording from and micro-stimulating small (~100-200m diameter) peripheral nerves in pre-clinical animal models. Though this project will be focused on creating a device for electrical interfacing, this project may also inform the development of new optical, thermal, ultrasonic, or chemical interfaces that must meet similar biomechanical challenges. More generally, placing implantable probes on or nearby the soft, delicate tissues of the body is a major scientific challenge, thus we anticipate this research and technology development will impact biomedical research and implantable device development broadly. !